The purpose of this core is to provide a phenotypic validation of the genetic manipulation made under several subprojects. This core will provide neurobiological evaluations of transgenic and partial trisomic lines constructed to provide over-expression of single or multiple genes found on human chromosome 21. Behavioral, histological and neurochemical and studies will be carried out to identify the specific neurobiological effects of over-expression of these genes to determine what genes singly or in combination may account for the mental retardation or other neurobiological outcome exhibited in Down syndrome. The core will also provide an assessment of cholinergic and glutamatergic development in Ts65Dn mice and will evaluate the effects of the pharmacological manipulations in Dr. Moran's project. The proposed core represents a significant expansion from what had existed under the previous program. This expansion of the core is consistent with the changing priorities and focus of the program. The core has two components which take advantage of the expertise of the investigators. The behavioral and pre-synaptic neurochemical evaluations will be carried out in Dr. Moran's laboratory within the Department of Psychiatry at Johns Hopkins. Dr. Blue will assess brain morphology and immunohistochemical techniques at the Kennedy Krieger Institute.